196 PASSIVE IMMUNIZATION. 



The Theobald Smith Phenomenon. 



Theobald Smith observed that guinea-pigs injected with neutral mixtures of diphtheria 

 toxin and horse's antitoxic serum would be killed if after an interval of several weeks they 

 were given a subcutaneous injection of normal horse's serum (several cubic centimeters). 



Otto and others showed that both of these phenomena, above described, are identical 

 in their principle; thus, that of Arthus can be likewise induced after a single injection of 

 horse's serum if the first dose is small, and if the interval between the first and second 

 inoculation is sufficiently long (about three weeks or more). 



Anaphylaxis is specific; that is the animals made anaphylactic against horse's serum 

 will produce a reaction only, when subsequently injected with horse's serum and not 

 when any other, like bovine serum is used. Even a single injection of 0.001-0.004 c.c. 

 of horse's serum suffices according to Rosenau and Anderson, to produce anaphylaxis in a 

 guinea-pig. The greater the amount of serum given at the first inoculation, the longer is 

 the period which must elapse before the onset of the state of hypersusceptibility. With 

 doses of several cubic centimeters, this interval is two to three months in duration. 



The effect of the second injection depends largely upon the method of its administra- 

 tion. Given subcutaneously or intraperitoneally, 5 to 6 c.c. are required to bring about 

 acute death of the animal, while by the intravenous or intracerebral route fractions of a 

 cubic centimeter usually suffice. 



Animals which recover from their anaphylactic condition after the second 



Antiana- injection, become antianaphylactic, i.e., they do not react to further 



phylaxis. injections of the same serum or proteid solution. Such immunity appears 

 two hours after the recovery from the anaphylactic shock. 



In order to prevent anaphylaxis in animals, Besredka and Steinhardt advise the use 

 of a very small amount of serum for the second injection, followed by a larger dose in 

 twenty-four hours; or an injection of a very large dose during the period of incubation, 

 best on about the eighth day. 



Passive Anaphylaxis. 



Anaphylaxis like immunity can be transmitted from one animal to another by means 

 of the serum. Passive anaphylaxis is best demonstrated by injecting the anaphylactic 

 serum subcutaneously, followed in twenty-four hours by the inoculation of the respective 

 antigen. 



No absolutely decisive explanation has as yet been offered for the anaphy- 

 lactic status. It seems certain, however, that its phenomena are closely 

 associated with the process of immunity. 



Since the term immunization usually implies a beneficial process, while 

 anaphylaxis in most instances represents a situation of an injurious nature, 

 v. Pirquet recommended the term "allergic" to designate the reactive 

 changes which an organism generally exhibits after infection or injection of 

 an antigen. The " allergic phenomena" are divided into those associated 

 with diminished susceptibility, i.e., prophylaxis; and those with increased 

 sensitiveness, i.e., anaphylaxis. 



Besredka adheres to the view that the anaphylactic syndrome especially expresses an 

 insult to the central nervous system. He was able to show that susceptible guinea-pigs 

 when etherized, will bear the second inoculation of the serum perfectly well. 



v. Pirquet and Schick, Friedberger and others, consider the precipitin action as the 



